Tag Archives: mthfr mutation basics

I am so happy to report that the MTHFR C677T mutation now comes with a superpower, and it’s prostate cancer protection. It’s not quite X-Men worthy and I have to admit mind control might be a bit cooler, but protection against one of the most common forms of cancer is nothing to scoff at.

The association between MTHFR mutation and prostate cancer has been unclear, with some studies showing increased risk, some studies showing no change and some showing decreased risk, so the information can be difficult to wade through. A recent research study conducted in Shanghai and published in Scientific Reportsshows that C677T polymorphisms, whether they are homozygous or heterozygous, are actually protective against prostate cancer although they are quick to say that this study was conducted on the Han Chinese population in Shanghai and that the results may be different for different ethnic groups.

The study shows that intracellular homocysteine levels are slightly elevated when the C677T mutation is present and that elevated homocysteine actually helps to encourage damaged cells, such as precancerous and cancerous cells, to die off the way they should, rather than proliferating into full blown cancer. In unfortunate news, a recent meta-analysis published in Genetics and Molecular Research, showed that this association may not exist in caucasian males and that in this population C677T mutation may not have any effect on prostate cancer. Interestingly, this same meta-analysis showed that the A1298C mutation might have a slight protective effect against prostate cancer in European males.

The most important thing to remember, is that almost every mutation that exists in humans or animals has a double edge – it often has some drawbacks, but typically benefits too or the members of the population with that mutation would die out. MTHFR seems to be, if anything, becoming more common so I suspect in years to come we will find many other benefits associated with it.

Overmethylated vs. undermethylated seems to be one of those things that everyone defines a different way, so let’s talk about it and see if we can bring some clarity. The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them. These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation). Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Overmethylation MTHFR

This is less common than undermethylation. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Overmethylation in this context means that the methylation cycle as a whole is sped up, or downstream reactions that use SAMe (the ultimate product of the methylation cycle) are compromised in such a way that there is too much SAMe floating around wanting to methylate something.

Clinically overmethylators are more likely to have agitated or anxious conditions. Frequently panic or anxiety attacks (64% of panic/anxiety clients at the Walsh Research Institute), paranoid schizophrenia (52% of paranoid schizophrenic clients at WRI were overmethylators), ADHD (28%), behaviour disorders (23%), depression (18%). Depression can occur in under, normal or over methylators but 18% of depressed clients of Dr. Walsh are overmethylators.

Mutations most likely to contribute to overmethylation are AGAT, GAMT, CBS and MT. MTHFR mutation usually pushes towards undermethylation (but I myself am compound heterozygous MTHFR and an overmethylator) Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.

Other contributing factors are impaired creatine synthesis. This is because Approximately 70% of the SAMe from the methylation cycle is used by creatine synthesis, so if this is impaired the SAMe is used more slowly. This can be due to genetic factors (AGAT or GAMP) or due to deficiencies of arginine or glycine. Also impaired cystathione synthesis, or other polymorphisms in methyltransferase SNPs that account for the rest of the SAMe use.

Overmethylation leads to excessively high activity of dopamine, norepinephrine and epinephrine in the brain.

If this reminds you of you, you could be overmethylated. A photograph of Robin Williams taken by Michael Dressler in 1979, later used as a cover photo for Time magazine to highlight Williams.

Adverse reaction to SSRI drugs, SAMe or methionine (typically all make anxiety or depression much much worse.

An easy way to picture this type is by using Robin Williams as an example.

Is Overmethylated the Same as Over-supplemented?

No, although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might be “overmethylated” if you are taking too much 5-MTHF or SAMe. I feel that these are different things entirely. If you have a tendency to be overmethylated then certainly you would probably feel worse taking something like SAMe, but even without that you are still an overmethylator (in my opinion). Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Overmethylated. Now What?

Interestingly the best way to balance the consequence of overmethylation, is still 5-MTHF. This seems strange, because it is also the answer if you’re’ undermethylated, but the effects are actually coming from a different mechanism. Folate actually reduces activity at serotonin, dopamine and norepinephrine synapses. 5-MTHF is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement. Trouble taking the supplement is surprisingly common, although I think less common clinically in overmethylators (in my experience) than in undermethylators. Niacin or niacinamide can also be helpful for overmethylators as they quench some of the excessive methylation. Again, start slowly.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period. Here’s a whole post on it. Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.

MTHFR mutation discussions can quickly turn into Greek and the topic of overmethylated vs undermethylated MTHFR is one of the Greekest. It seems like no two resources on the internet are talking about the same thing when they talk about it and so overmethylation and undermethylation are strange, kind of meaningless words because at the end of the day it feels like nailing jello to a wall. So let’s see if we can sort some of this out.

Whose Idea Is This? I’m Following The Walsh Research Institute

The terms overmethylation and undermethylation make the most sense to me as the Walsh Research Institute uses them. These are general physical tendencies based on the sum of your genetics, nutritional status and body burden. There isn’t one gene or genetic defect alone that can account for them – so just because you have an MTHFR C677T mutation doesn’t actually mean you’re over or under methylated (although it would be one factor that might push the balance to undermethylation). Dr. Walsh describes one’s methylation status as being like a tug of war between opposing factors. Many of those are genetic and some are nutritional or environmental.

Undermethylation MTHFR

This is the most common state. According to Dr. Walsh’s research, 70% of the population are normal methylators, 22% are undermethylators and 8% are overmethylators. Undermethylation indicates that the methylation cycle as a whole is slowed down enough that the end product, SAMe, is typically inadequate and thus causes symptoms.

Clinically undermethylators are more commonly autism spectrum (98% of autism spectrum clients at the Walsh Research Institute), antisocial disorder (95% of antisocial clients at WRI were undermethylators), schizoaffective disorder (90%), oppositional defiant disorder (85%), anorexia (82%), and depression (which can occur in under, normal or over methylators but 38% of depressed clients for Dr. Walsh are undermethylators).

Mutations most likely to contribute to undermethylation are MTHFR (C677T especially, but also A1298C), MS, BHMT, MAT and SAHH. Remember that the presence of one or more of these mutations isn’t enough to say if you’re an over or under methylator. The combination of all of your genetic factors as well as your nutritional state must be taken into account. The best way to determine is through symptoms and traits.

Other contributing factors are histamine overload and protein deficiency, as well as frank deficiency of folate.

Highly competitive? You might be undermethylated

Symptoms and traits of undermethylation include:

Strong willed

Highly competitive at sports or whatever matters to them

Obsessive/compulsive tendencies

Addictive tendencies (more likely to be addicted with less exposure than a normal methylator)

High sex drive

Tend towards high accomplishment and usually a high achieving family

Appear calm and well controlled (possibly over-controlled) but inner tension is high

Is Undermethylated the Same as Under-supplemented?

No! Although it seems that in a lot of popular literature on the subject people use the term interchangeably. So often you’ll see someone say that you might still be “undermethylated” if you aren’t taking enough 5-MTHF. I feel that these are different things entirely. If you have a tendency to be undermethylated then certainly you will probably need to take 5-MTHF, but even once you’re taking enough you are still an undermethylator (in my opinion), you’re just taking the right protocol. Likewise taking too much 5-MTHF, doesn’t make you suddenly “overmethylated” it just means you’re taking too much.

Okay! I’m Undermethylated. Now What?

Absolutely the best way to enhance the methylation cycle is by taking 5-MTHF, or 5-L methyltetrahydrofolate. This is the active form of folic acid, and you can also get it from foods, especially if you have some trouble taking the supplement. Trouble taking the supplement is surprisingly common, typically it is an adjustment reaction to actually enhancing the methylation cycle because this changes neurotransmitter levels, encourages detoxification and encourages more than 80 reactions in the body that are methylation dependent. So some adjustment reaction when you’re first taking 5-MTHF is normal and actually a good sign that things are changing in your body. There is one BIG EXCEPTION TO THIS, and that is if you are undermethylated and have depression.

I Want to Start Taking 5-MTHF. How Do I Make This Easy?

Any time you start taking 5-MTHF, or increase your dose, there will be an adjustment period. Here’s a whole post on it. Just remember, start with a low dose and increase really slowly. This is changing the way your neurotransmitters work and doing some heavy detox work, so it’s vital not to overdo it because that is crazy-making. Start low and go slow.

HELP! I’m An Undermethylator and I Have Depression.

My next post is going to be all about this because UNDERMETHYLATORS WITH DEPRESSION DUE TO LOW SEROTONIN CAN’T TOLERATE 5-MTHF, FOOD SOURCES OF FOLATE OR FOLIC ACID AT ALL. That’s a really big deal! Depression is typically characterized by low serotonin states and unfortunately 5-MTHF (or any folate or folic acid). The short explanation for this is that folate, 5-MTHF and folic acid all increase the activity of the transport protein that re-uptakes serotonin into the cell. Essentially this is the opposite of a serotonin reuptake inhibitor (like prozac), it’s a serotonin reuptake promotor – meaning it makes the serotonin you have far less effective because it clears it out more quickly. There will be a whole post on this – I promise!

This week I had the lovely opportunity to be on Blog Talk Radio with Erin Chamerlik, The Real Food Revivalist- see getbetterwellness.com. Her listeners wanted to know a little bit more about MTHFR mutation. You can listen to the recording here:

MTHFR mutations are just starting to be recognized as an issue and so more and more doctors are testing, but what happens if your doctor tells you that you’re homozygous for MTHFR A1298C? They might as well be speaking Greek! So here’s the skinny on what that really means. Also here’s a post about MTHFR mutation basic in general.

MTHFR A1298C Terminology Basics (or as basic as we’re going to get with genetics).

The simplest level of information here is just the plain genetics. Here are some quick factoids to get us started:

MTHFR is the short name for the genes that code for the enzyme that changes folic acid to the active form that your body uses (the long name is methylfolate reductace).

1298 is the marker for one particular MTHFR gene.

The official genetics labeling of this gene is Rs1801131. Sigh.

You get one copy of this gene from your mother and one from your father, so there are two possible copies that can be either “normal” or “mutant”

If you inherited one good copy and one bad copy that’s called “heterozygous A1298C”

If you inherited two bad copies (one from each parent) that’s called “homozygous A1298C”

A…C stand for the bases that you actually have. A = adenine C = cytosine. Bases are essentially the letters that spell out your genetic code. There are four of them commonly (C, T, A and G).

When this gene is “normal”or “wild type” (I love that name) it looks like MTHFR A1298A.

Heterozygous mutations (one good copy and one bad) are MTHFR A1298C because there is one normal A and one abnormal C Also occasionally written 1298AC.

Homozygous A1298C (two bad copies) can also be written as C1298C (because there are two abnormal copies with C instead of A). Occasionally you’ll also see it written 1298CC

Phew! So the take-away there is MTHFR A1298C means you have at least one bad copy of this gene, and if it’s called homozygous, or C1298C then you have two bad copies.

How Much of a Problem Is This?

The MTHFR A1298C mutation is considered less serious than the C677T mutation because it seems to cause less impairment to actual methylation function than C677T. That doesn’t in any way mean that it isn’t an issue. This mutation can still be a significant problem If you don’t have a good diet, don’t take supplements or burden your body with a lot of stressors like smoking, alcohol, drugs, sedentary lifestyle or high stress. If you get lots of dark green leafy veggies, legumes and other food sources of natural folate – see this post – then you’re probably already getting good methylfolate. If your diet isn’t up to scratch, then supplementation can be useful and here’s a whole post about that.

Heterozygous MTHFR A1298C is thought to have mostly normal MTHFR activity and homozygous MTHFR A1298C (C1298C) have about 65% normal activity (so 35% compromise). Normal activity refers to the way your body converts folic acid to 5-L-methyltetrahydrafolate (the active form) so that it can be used. Compromise in this case looks like a folate deficiency.

What Are The Health Risks of MTHFR A1298C Mutation?

According to SNPedia, which compiles research on genetics, A1298C mutants have been shown in at least one research study to have an increased risk for:

Midline defects such as:

Cleft lip

Cleft palate

Neural tube defects

Facial asymmetries

Cancers including:

Breast

Lung

Brain

Stomach

Head and neck

Kidney

Cardiac-related issues including:

Thrombosis (increased tendency to clot inappropriately)

High homocysteine levels (a heart risk)

Pre-eclampsia (dangerous high blood pressure in pregnancy)

Vascular dementia

Fertility issues including:

Multiple pregnancy loss

Low sperm count

Birth defects such as down syndrome

Neurological issues including:

Migraines

Autism

Alzheimer’s dementia

Mood and psychological issues including:

Depression

Anxiety

Schizophrenia

You’ll notice that this is quite a list, and it can be a little daunting to think about when you’re just learning about this. Most research doesn’t differentiate between the A1298C genetic variance and the C677T genetic variance so the list is the same for both mutations. We assume the risk is lower with A1298C because the folate metabolism is less strongly impaired, but that might not be correct.

What Do You Do About This?

Compromise with the MTHFR A1298C gene can have severe consequences so it’s important to work on getting good sources of natural folate from foods, which is generally useable by mutants, or 5-MTHF (5-methyltetrahydrofolate) which is already methylated so the genetic compromise doesn’t matter. As discussed in this article, I feel supplementation should be started slowly because for many mutants who haven’t had active folate very much in their lives it feels really strange when those active forms start showing up. There can be quite an adjustment reaction by your body.

Activated folate is used by your body to run enzyme pathways, to aid in some parts of normal metabolism, to help your body detoxify and even to methylate your DNA. The methylation cycle is also a big part of neurotransmitter manufacture, which explains the strong link to depression, anxiety, and mental disorders including addictions and even schizophrenia. If 5-Methylfolate isn’t there then your body does maintains those functions as best it can, but the things your body can’t do start to pile up. Starting supplementation means your body can start digging in that pile to clear up high priority items. This is exactly what we want, but if you start with high doses of a supplement then it’s a little like drinking from the firehose. Kind of out of control and not very pleasant.

A great way to start if you’re unsure, is with a folate-rich diet. I love this image because it kind of covers what we’re looking for. Hint – think dark greens and beans. 🙂

Is folate in foods safe in MTHFR mutants? In these foods YES! For MTHFR C677T or MTHFR A1298C mutants. Thanks to exhibithealth.com for the great image.

Can Mutants Become “Normal”?

If you’re a mutant (like me) then you’ll always be a mutant, but it doesn’t have to matter. Essentially as long as you’re getting enough of the active form of folate and taking care of yourself for the other consequences of the MTHFR mutation then the mutation doesn’t have to matter. If you aren’t taking care of yourself, then it matters a lot.

The bottom line is MTHFR A1298C mutations don’t have to mean anything at all as long as you supplement and have a good diet and lifestyle (here’s an article about a folate-rich diet for MTHFR mutants) I always suggest taking a little more care with yourself too. There are known health risks for things like clotting, fertility and cancers so it makes sense to take some precautions. Eat your fiber, do your exercises, get your sleep and generally treat yourself with high regard – shouldn’t we all anyway?

MTHFR mutations are just starting to be recognized as an issue and so more and more doctors are testing, but what happens if your doctor tells you that you’re homozygous for MTHFR C677T? They might as well be speaking Greek! So here’s the skinny on what that really means. Also here’s a post about MTHFR mutation basic in general.

MTHFR C677T Terminology Basics (or as basic as we’re going to get with genetics).

The simplest level of information here is just the plain genetics. Here are some quick factoids to get us started:

MTHFR is the short name for the genes that code for the enzyme that changes folic acid to the active form that your body uses (the long name is methylfolate reductace).

677 is the marker for one particular MTHFR gene.

The official genetics labeling of this gene is Rs1801133. Sigh.

You get one copy of this gene from your mother and one from your father, so there are two possible copies that can be either “normal” or “mutant”

If you inherited one good copy and one bad copy that’s called “heterozygous C677T”

If you inherited two bad copies (one from each parent) that’s called “homozygous C677T”

C…T stand for the bases that you actually have. C = cytosine, T = thymine. Bases are essentially the letters that spell out your genetic code. There are four of them commonly (C, T, A and G).

When this gene is “normal” it looks like MTHFR C677C.

Heterozygous mutations are MTHFR C677T because there is one normal C and one abnormal T. Also occasionally written 677CT.

Homozygous C677T can also be written as T677T (because there are two abnormal copies with T instead of C). Occasionally you’ll also see it written 677TT

Phew! So the take-away there is MTHFR C677T means you have at least one bad copy of this gene, and if it’s called homozygous, or T677T then you have two bad copies.

How Much of a Problem Is This?

This can be a significant problem If you don’t have a good diet or you don’t take supplements. If you get lots of dark green leafy veggies, legumes and other food sources of natural folate – see this post – then you’re probably already getting good methylfolate. If your diet isn’t up to scratch, then supplementation can be useful and here’s a whole post about that.

Heterozygous MTHFR C677T have about 65% normal MTHFR activity (so 35% compromise) and homozygous MTHFR C677T (T677T) have about 30% normal activity (so 70% compromise). Normal activity refers to the way your body activates your folic acid so that it can be used, so compromise usually looks like a functional folate deficiency.

What Are The Health Risks of C677T Mutation?

According to SNPedia, which compiles research on genetics, C677T mutants have been shown in at least one research study to have an increased risk for:

Midline defects such as:

Cleft lip

Cleft palate

Neural tube defects

Facial asymmetries

Cancers including:

Breast

Lung

Brain

Stomach

Head and neck

Kidney

Cardiac-related issues including:

Thrombosis (increased tendency to clot inappropriately)

High homocysteine levels (a heart risk)

Pre-eclampsia (dangerous high blood pressure in pregnancy)

Vascular dementia

Fertility issues including:

Multiple pregnancy loss

Low sperm count

Birth defects such as down syndrome

Neurological issues including:

Migraines

Autism

Alzheimer’s dementia

Mood and psychological issues including:

Depression

Anxiety

Schizophrenia

You’ll notice that this is quite a list, and it can be a little daunting to think about when you’re just learning about this.

What Do You Do About This?

Compromise with the MTHFR C677T gene can have severe consequences so it’s important to work on getting good sources of natural folate, which is generally useable by mutants, or 5-MTHF (5-methyltetrahydrofolate) which is already methylated so the genetic compromise doesn’t matter. As discussed in this article, I feel supplementation should be started slowly because for many mutants who haven’t had active forms of folate very much in their lives it feels really strange when those active forms start showing up and there is a whole lot of adjusting by your body. This activated folate is used by your body to run enzyme pathways, to aid in some parts of normal metabolism, to help your body detoxify and even to methylate your DNA. If it isn’t there then your body does what it can, but what it can’t do starts to pile up. Any time you start supplementation then your body starts digging in that pile to clear up high priority items. This is exactly what we want, but if you start with high doses of a supplement then it’s a little like drinking from the firehose. Kind of out of control and not very pleasant.

A great way to start if you’re unsure, is with a folate-rich diet. I love this image because it kind of covers what we’re looking for. Hint – think dark greens and beans. 🙂

Is folate in foods safe in MTHFR mutants? In these foods YES, even for MTHFR C677T mutants. Thanks to exhibithealth.com for the great image.

Can Mutants Become “Normal”?

If you’re a mutant (like me) then you’ll always be a mutant, but it doesn’t have to matter. Essentially as long as you’re getting enough of the active form of folate then the mutation doesn’t have to matter. If you aren’t, then it matters a lot.

The bottom line is MTHFR C677T mutations don’t have to mean anything at all as long as you supplement and have a good diet (here’s an article about a folate-rich diet for MTHFR mutants) I always suggest taking a little more care with yourself too. There are known health risks for things like clotting, fertility and cancers so it makes sense to take some precautions. Eat your fiber, do your exercises, get your sleep and generally treat yourself with high regard – shouldn’t we all anyway?

The quick answer is no. You probably don’t need genetic testing for MTHFR even if you suspect there’s a problem, but you still might want it. If that isn’t enough information, then read on!

Why Genetic Testing for MTHFR Might Not Be Necessary

For many people with the MTHFR mutation, there is a simpler, more medically recognized, cheaper test called homocysteine. For the majority of MTHFR folk homocysteine levels become elevated because of the lack of usable folate. This test is cheap and you won’t have any trouble talking your doctor into ordering it. Bonus!

Dr. Charis Eng, a prominent geneticist at the Cleveland Clinic makes a great argument that really, if you suspect a mutation, you can just take the methyl-folate and appropriate B vitamins and you’re done. No harm, no foul. In short you don’t need genetic testing because you can just go ahead and take the vitamins. Good point Dr. Eng!

Even with a complete genetic profile run through every methylation panel out there, finding the right dose of methylfolate for you is still a lot of educated guessing and trial and error. Testing might give you guidelines, but you really still have to start slowly and work your way up.

Are There Reasons Why I Should Do Genetic Testing for MTHFR?

There are certainly some compelling reasons to get the testing done, not the least of which is your kiddos.

With genetic testing, especially the complete information gathered from 23andme, you have a better idea of not only your MTHFR status but also about all of the other genes that play into the methylation and detoxification process. It helps us understand all of the ways you might be compromised and so gives a more solid starting place. (If your doctor runs the MTHFR test then really you’ll only have info about MTHFR, not about any of the related genes).

If you have kids or are thinking about having kids it really helps to know what their chances are of picking up bad copies of these genes from you. If you know there might be an issue then you can start helping them find balance while they’re young (or even before they’re born).

What are the Options for Genetic Testing for MTHFR from my MD?

MDs have started ordering testing – especially if you have some strange blood coagulation issues, if you’ve had repeat miscarriages, or if you pester the hell out of them. Insurance will only cover testing if it’s “medically necessary” – and typically that is only if there are weird blood clotting issues. Just keep that in mind. There are only a few MTHFR tests that are FDA approved, and none of them are intended for people with anxiety, depression, inflammatory disorders, etc… They still work, but it can be hard to talk your doctor into ordering them. These are all spendy if insurance isn’t paying for them, so ask your doctor before you have them run.

Is there Genetic Testing for MTHFR that You Can Run Yourself?

This is by far my favorite option, simply because you get so much for so little money (relatively speaking). It’s 23andme. They provide you with a saliva test kit that you mail in and in about a month you get a whole heap of information online including info about your ancestry, about your genetic response to certain pharmaceutical drugs, and about different health risk factors. At the time of this article it’s $199 US or $249 Canadian. Typically this is cheaper than the FDA approved testing and there’s far more information. Embedded in all of this information is your MTHFR status, although it’s hard to find unless you run your results through some kind of interpretation engine.

In terms of interpretation for MTHFR there are a couple that I like. The one I suggest most often is called “genetic genie” and they have a methylation panel (that uses the raw data from 23andme) and a detox panel (again with the 23andme). The reports are very complete and they ask for a modest donation. Freaking awesome.

Another good option are the reports from MTHFR support. This report shows more gene snips than the genetic genie report, but gives less information about each one. It also costs a little more (but still totally reasonable). Like genetic genie, MTHFR support doesn’t actually test the genetics – you need 23andme for that – they just interpret the information.

At the end of the day you can get genetic testing for MTHFR if you choose, but you don’t really have to – you can also just go ahead and start to supplement if you suspect an issue. I’m a total geek for information, so of course I got mine done by 23andme (I’m 3% neanderthal, in case you were wondering, because obviously that is information everybody needs). I’m glad I know, but honestly it really didn’t change too much about the way I approach my dosage of methylfolate. It’s just better information for me (and for my kiddos).

The question of folate in food safe for MTHFR mutants has, like everything else about MTHFR, a complex answer: yes and no. Sigh. But actually there’s a pretty easy split, and that’s between foods naturally high in folate, and foods fortified with folic acid.

Foods Naturally High in Folate

This list is all awesomeness. These are great healthy foods that most people want to incorporate into their diet but many of us mutants (MTHFR mutants that is) hesitate because of the folate content. Great news folks – naturally occuring folate is actually not a problem with the MTHFR mutation. Here’s the thing – what we call “folate” isn’t actually just one thing. In nature it’s a collection of related molecules in the family of pteroylglutamates (say that three times fast). Folate can be used directly by the human body, it doesn’t have to be converted into anything and so with or without a MTHFR mutation we can use folate well.

We use folate to synthesize, repair and methylate DNA, and as a cofactor in a number of reactions in the human body. It’s especially important in periods of rapid growth and cell division – so infancy, growth spurts and pregnancy. We also use it to make our red blood cells and deficiency is one of the causes of anemia.

Is folate in food safe for MTHFR mutants? In these foods YES. Thanks to exhibithealth.com for the great image.

The answer to the question ‘Is NATURALLY OCCURING folate in foods safe for MTHFR mutants?’ Is a resounding YES.

Foods Fortified with Folic Acid

Here’s where the MTHFR group get tripped up. Often ‘folate’ and ‘folic acid’ are used interchangeably to refer to the same thing, because they theoretically do the same things in the body. Except for MTHFR mutants they really don’t do the same thing because we have varying degrees of impairment with the enzyme that converts folic acid to folate. This means that MTHFR mutants really can’t count folic acid, which is the synthetic, lab-created, oxidized form of folate which is really not found so much in nature. This requires functioning MTHFR genes to be converted into a usable form of folate. If you don’t have good function of your MTHFR genes (and just a note – we all have some function, we’re just impaired) then you don’t get to use this form very well.

Folic Acid ≠ Folate

The issue with eating a lot of foods fortified with folic acid for an MTHFR mutant is that the folic acid competes at receptor sites with natural folate that is coming from your diet. This means the synthetic folic acid makes the natural folate less effective because much of the time the synthetic (unusable) form is clogging up the folate receptors.

Foods Most Likely to Be Fortified with Folic Acid (Unsafe for MTHFR Mutants):

The best strategy to make your foods MTHFR friendly is to eat whole foods, natural unfortified whole grains, and skip the fortified garbage. There are many dangers of folic acid (and not just to MTHFR mutants – we’ll talk about that later) so avoid it wherever possible and add naturally-occurring folate-rich foods into your diet wherever you can. One more time: Is folate in food safe for MTHFR mutants? You betcha, but folic acid isn’t.

MTHFR mutation is a huge factor in physical and mental health but we’re still learning the basics because it’s all very new research so the best dose of methylfolate for MTHFR mutants isn’t really a straight answer. The good news is there are lots of ways to read your body and to learn the best dose of methylfolate for YOU. If you’re a little fuzzy on this whole MTHFR thing, then check out this post on the MTHFR basics. This will give you a good framework for the whole conversation – also if you suspect you have the mutation, read more about how to know you’re a mutant here. If you, like me, already know that you’re a mutant then let’s tackle the hard problem of finding the best way to compensate for your body. Finding the right dose of methylfolate can help to reduce anxiety and depression, stabilize mood, boost fertility, protect your heart and cardiovascular system and generally keep your body at peak performance so it’s important to take some time and do this the right way.

Finding the Best Dose of Methylfolate is a Process of Trial and Error

I wish there was just one answer – this is the right dose, but sadly it all comes down to what is the right dose for your body. First off, I never suggest taking methylfolate by itself without any other B vitamins. The B vitamins all have overlapping functions and so it’s important to have decent doses of all of them. Typically though I start clients with a B complex that has a reasonably low dose of methylfolate – like maybe 400 mcg. I really like the one from Pure Encapsulations called B Complex Plus. It’s basic, simple, and most people – even hard core mutants – tolerate it pretty well, but I’m not married to it. Any good multi-B with a low-dose methylfolate will do or you can look for a multivitamin that has methylfolate in it like Thorne Research Basic Nutrients. Occasionally even this low dose creates a bad reaction – if that happens then we’ll have to start with a low dose MTHF by itself and split the capsule apart but this is the option of last resort. First, let’s try the low dose B complex or multivitamin and see what happens.

Keep in mind the first three days of any MTHF might be difficult and there may be some adjustments. You may notice that you’re a little agitated, or anxious, or depressed or just feel a little spacy or off. With any luck that should pass pretty quickly and we’ll wait for things to stabilize before increasing the dose.

If the Low- MTHF B Complex or Multi Works for You

Great! We’re on the right track. Even if this is the right dose for you there might be a few odd adjustment days in the beginning – that is totally normal. Just wait until everything settles down and see how you’re feeling. Typically with this low dose people may notice a small spike in energy or a little boost to mood, but often it isn’t enough methylfolate to start to touch the issues – that’s okay because it’s enough to get the ball rolling. The next step would be to add a 1 mg (1000 mcg) MTHF by itself to the B complex you’re already taking. We’re looking to make forward progress without rocking the boat too much. Each time you increase the dose there may be another adjustment reaction as your body gets used to things, so try to stick it out for 3 days before you make a final judgement about it.

If the Low-MTHF B Complex or Multi DOESN’T Work for You

Then we switch to plan B. Plan B is a little messier and more tedious, but it could make all the difference for how you’re feeling on a day-to-day basis. Start with a 1mg MTHF – I prefer a capsule so that you can just open it and portion out the powder (instead of trying to cut or crush a tablet). In this situation start with 1/4 of the capsule – easiest is mixing it with some peanut butter, applesauce or yogurt and taking it that way. It tastes pretty gross, but hopefully you can hide it in something. Again count on about 3 days of adjustment, but we’re starting with very low doses here so hopefully that will be fine and if it’s still too much then you can cut it down even further. Once you get to the dose you can tolerate, keep it there for a couple of weeks and try to slowly increase. By now your body has started to process some of the back-log of work so it might be easier to tolerate a bigger dose. Now would be a great time to try going to the B complex with MTHF or multi with MTHF because you do still need all those other B vitamins.

What to Do If You Can’t Tolerate ANY MTHF?

Yup – I’ve seen clients like this. They take the tiniest amount and spiral into depression or anxiety attacks or start to feel itchy. Not fun at all! In this situation it’s tiny-dose niacin to the rescue. For whatever reason taking about 10-50 mg of niacin – this is usually 1/10th or even less of a 500 mg niacin tablet. It’s a tiny dose, but for many people it really helps to ease the transition into MTHF. Start again with a small dose from the opened MTHF capsule (maybe 1/4) and add a tiny shaving off the niacin capsule and see how you do. The niacin seems to buffer things a big so that the MTHF is a little bit easier to tolerate – again it’s about helping your body to do some of the work that has piled up in the absence of activated B vitamins. If niacin doesn’t help then sometimes hydroxycobalamin will. This is a little bit mysterious because you’d think it would be methylcobalamin (the methylated form of B12 which MTHFR mutants also have a hard time making). Oddly, the hydroxycobalamin form seems to be the most helpful when you’re starting MTHF dosing and when niacin doesn’t take the edge off, a lot of times hydroxycobalamin will. Do you see what I mean about trial and error?

Methylation, it’s complicated. The best dose of methylfolate is out there for you – you just have to find it. Thanks to flickr user Franklin Park Library for the image.

How Do I Know I Found The BEST Dose of Methylfolate?

We are doing all of this to help you feel better as a whole human. Methylating your B vitamins or taking methylfolate is supposed to help boost your energy, stabilize and elevate your mood, help your body with detox reactions and reduce a wide variety of symptoms over time. So how do you know you’re’ at the perfect dose for you? Well – you should feel better. Keep in mind the prescription methylfolate comes in 7 mg and 15 mg doses (deplan). Those are a whole lot bigger than the doses we’re starting with above so when you find a good starting dose for yourself then stay there for a couple of weeks. If you’re feeling fine and stable but not a lot of improvement then try a higher dose and see how you feel with that. For everyone there is a sweet spot where they feel better and more energetic, but not anxious or wound up. Keep in mind every time you increase dose those first 2-3 days may be a little bit odd. Don’t judge by those days.

Things to Remember:

You need all the B vitamins, not just methylfolate so don’t leave those out of the mix. A good methylated multi or methylated B complex is a great foundation to start with.

Methylation affects neurotransmitter formation, inflammation and detoxification so lots of random symptoms can pop up when you increase the dose. Give it a few days before you make judgements.

Increasing doses slowly is easier for your body to tolerate than just dumping a high dose in all at once.

Tiny doses of niacin can help smooth out the transition.

Hydroxycobalamine, a form of B12, can also help to make taking MTHF a little easier.

Every body is different so the best dose of methylfolate for you could be completely different from the perfect dose for someone else.

Every MTHFR mutant has mutations in different spots and combinations plus a whole host of other genetics to deal with. Don’t get discouraged – there is always a perfect solution, you just have to find it. Generally though the more mutations you have the longer it might take to find the right balance.

Methyl donors like Trimethylglycine (TMG) which is also called betaine anhydrous can also support this process by donating methyl groups for your newly-functioning methylation pathways to use.

Riboflavin-5-phosphate also supports methylation and homocysteine metabolism (which tends to build up if you’re not a great methylator) so sometimes a small dose of this will help things out as well. It should be in a good B complex.

It’s important to avoid sources of folic acid (which there are many – think all of the “enriched” grain products like cereals, breads, pasta) including multivitamins with folic acid or vitamin-enhanced foods. Plain old folic acid will compete with the methylfolate you’re taking and make it harder for those pathways to work.

Specialty Methylation Products

There are a few great methylation products out there that have a combo of supportive ingredients. One of my favorite is Methyl-Guard Plus by Thorne Research, which combines a reasonably high dose methylfolate with methyl-B12, TMG and riboflavin-5-phosphate. It can be a high dose to start with though, so especially if you have a few mutant genes it’s a good idea to start with the lower dose products and work your way up. There is no sense shocking your body. Too high a dose can cause as many problems as too low a dose so it’s important to find your sweet spot.

The bottom line is that this is no different from any other aspect of health. You need to find the right thing for YOUR body and there is no one size fits all. The best dose of methylfolate for you is out there – you can find it. I feel like the biggest thing is to ease your way into it and not over-flood your body. Start slow and work your way up – better to get there slowly than to give up because you felt so bad when you tried the high dose.

I’m amazed at how many people are coming into my office with MTHFR mutations, and also at how difficult it can be to actually understand the MTHFR mutation basics. So let’s start from the beginning and go from there.

What is MTHFR? Why Do I Keep Hearing About It?

MTHFR, just to be confusing, is the name of both a gene and the enzyme which that gene helps your body to make. We call it MTHFR because the actual name, methylenetetrahydrofolate reductase, is just ridiculously long and cumbersome. This enzyme helps your body to methylate. If your genes have a mutation it means that the enzyme they’re supposed to make turns out just a little bit wrong. You still make the enzyme it just isn’t exactly the right shape and so it works differently from normal. It’s become kind of a buzzword these days simply because we’re discovering that it is more common than we thought and if you happen to be a mutant (like I am) then you may be at greater risk for a number of health problems. We’ll get to those in a second.

What Does the MTHFR Enzyme Do?

The short answer is that this enzyme methylates. Since the short answer sounds like something nobody cares about, let’s also talk about a long answer. Methylation means that you add a “methyl group” which is essentially a carbon bonded to three hydrogen that looks, appropriately, like mutant mickey mouse ears. This sounds highly anticlimactic, but actually helps your body to do almost everything, like replicating and using your DNA, activating your B vitamins, detoxifying toxic substances and a whole host of other things.

What Are The Possible MTHFR Mutations?

There are TWO MTHFR genes, the MTHFR-C gene and the MTHFR-A gene and you have two copies of each of these (one from your mother and one from your father). This means there is a whole variety of ways that things could go wrong… Let’s look at those here:

Possible good and bad copies of the MTHFR gene

This means that there are two genes, each with two copies and you could have good or bad copies of one or both… So:

All possible variations of MTHFR gene combinations.

The basic rule is that the more bad copies of the gene you have, the more likely you are to have negative health effects from those genes. The good news is the more bad copies of the gene you have, the more benefit you can get out of working to improve your body’s methylation ability.

Can I Fix a MTHFR Gene Mutation?

Yes and no. You are born with a set of genes and you’ll die with the same set – nothing can change your genes. That sounds like bad news, but the good news is that we can get around a slow enzyme pathway – usually by supplementing the methylated form of B vitamins (so that it doesn’t matter if your genes can’t convert them) and also methyl donors. MTHFR mutation can make your life miserable, but if you learn to deal with it correctly it can also be overcome.

Poor methylation is becoming a common topic in medicine simply because we’re realizing how common these mutations really are and how great an impact on health they have. Learn more about some of the conditions caused by this mutation here, and about some of the problems you can run into taking methylated B vitamins here. There is so much more to this story, but at least we’ve covered the MTHFR mutation basics here. If you suspect a problem, get tested and talk with a doctor who knows about it because that will be the quickest path forward.

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Amy Neuzil is a Health Coach and Naturopath and not a Medical Doctor or Doctor of Osteopathy. All information on dramyneuzil.com is written from a naturopathic perspective. While Amy and dramyneuzil.com strive to have the most accurate information possible, we do not provide medical or health care advice. Please consult your physician before starting any new supplements or treatments and for any medical questions you may have.